NM_007103.4(NDUFV1):c.1157G>A (p.Arg386His) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000592779.13

Allele description

NM_007103.4(NDUFV1):c.1157G>A (p.Arg386His)

Genes:

LOC126861242:CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:67379204-67380403 [Gene]
NDUFV1:NADH:ubiquinone oxidoreductase core subunit V1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_007103.4(NDUFV1):c.1157G>A (p.Arg386His)

HGVS:

NC_000011.10:g.67611973G>A
NG_013353.1:g.10122G>A
NM_001166102.2:c.1130G>A
NM_007103.4:c.1157G>AMANE SELECT
NP_001159574.1:p.Arg377His
NP_009034.2:p.Arg386His
NC_000011.9:g.67379444G>A
NC_000011.9:g.67379444G>A
NM_007103.3:c.1157G>A
NM_007103.4(NDUFV1):c.1157G>AMANE SELECT
p.Arg386His

Protein change:

R377H

Links:

dbSNP: rs536758576

NCBI 1000 Genomes Browser:

rs536758576

Molecular consequence:

NM_001166102.2:c.1130G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007103.4:c.1157G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000700634	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Nov 28, 2016)	germline	clinical testing	Citation Link,
SCV002032668	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 24, 2023)	germline	clinical testing	Citation Link,
SCV002247077	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 21, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 20818383, 35482246, 26345448, 26024641, 29353736, 29948731, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000700634

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Nov 28, 2016)

germline

clinical testing

Citation Link,

SCV002032668

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 24, 2023)

germline

clinical testing

Citation Link,

SCV002247077

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 21, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency.

Calvo SE, Tucker EJ, Compton AG, Kirby DM, Crawford G, Burtt NP, Rivas M, Guiducci C, Bruno DL, Goldberger OA, Redman MC, Wiltshire E, Wilson CJ, Altshuler D, Gabriel SB, Daly MJ, Thorburn DR, Mootha VK.

Nat Genet. 2010 Oct;42(10):851-8. doi: 10.1038/ng.659. Epub 2010 Sep 5.

PubMed [citation]

PMID:: 20818383
PMCID:: PMC2977978

Compound heterozygous mutations of NDUFV1 identified in a child with mitochondrial complex I deficiency.

Tang X, Xu W, Song X, Ye H, Ren X, Yang Y, Zhang H, Wu S, Lan X.

Genes Genomics. 2022 Jun;44(6):691-698. doi: 10.1007/s13258-022-01260-x. Epub 2022 Apr 28.

PubMed [citation]

PMID:: 35482246

See all PubMed Citations (7)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000700634.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From GeneDx, SCV002032668.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a damaging effect on complex I activity (Varghese et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28441825, 29976978, 24365713, 25525159, 26345448, 31665838, 23562761, 21696386, 27126960, 20818383, Nurun2021[Article], 34740920, 35586607, 35482246, 35803560, 34807224, 26024641, 25615419, 22644603, 21364701, 28906460, 31324802, 36462614)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002247077.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 386 of the NDUFV1 protein (p.Arg386His). This variant is present in population databases (rs536758576, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of mitochondrial complex I deficiency (PMID: 20818383, 26345448, 35482246). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 496918). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NDUFV1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NDUFV1 function (PMID: 26345448). This variant disrupts the p.Arg386 amino acid residue in NDUFV1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26024641, 29353736, 29948731). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 8, 2024

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